Growing cutting-edge study has demonstrated the RNA m6A methylation’s critical role in regulating tumorigenesis and progression all over the world, while it is still a mystery whether RNA m6A methylation has a positive impact on breast cancer treatment. In this article, we utilize bioinformatics to analyze three data sets including TCGA-BRCA, GSE96058, and GSE25066 and discover that breast cancer samples could be divided into 4 subtypes, which are quiescent, m6A methylation, protein-binding, and mixed, clarified by the expression level of m6A-related genes. R-survival analysis results also prove that the survival rate of breast cancer samples of the four subtypes significantly varies and remarkable differences in the number of exons’ skip among the four subtypes can be seen according to the analysis of breast cancer gene expression characteristics. The degree of TP53 mutation and copy number loss is most obvious in the protein-binding subtype when it comes to tumor driver genes. Among the DNA damage repair genes, there is a sharp increase in the copy number of RAD54B of the protein-binding subtype, but fewer mutations in other DNA damage repair-related genes and copy number deletion is everywhere. Results of m6A methylation influencing on the proportion of infiltrated immune cells also indicate significant differences of the four m6A subgroups in macrophages M0 and mast cells resting which are closely correlated to patient prognosis. In addition, findings of the highest tumor stemness index and the lowest in the m6A methylated type in breast cancer samples can prove the critical role of the high expression of m6A reader protein in the progression of breast cancer.

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m6A甲基化在乳腺癌进展中的特征及相关性的生物信息学分析

越来越多的前沿研究表明，RNA m6A 甲基化在调节全球肿瘤发生和进展中发挥着关键作用，但 RNA m6A 甲基化是否对乳腺癌治疗具有积极影响仍然是个谜。在本文中，我们利用生物信息学分析了 TCGA-BRCA、GSE96058 和 GSE25066 三个数据集，发现乳腺癌样本可分为 4 个亚型，分别是静止亚型、m6A 甲基化亚型、蛋白结合亚型和混合亚型。 m6A相关基因的表达水平。R-survival分析结果也证明，四种亚型的乳腺癌样本的存活率存在显着差异，并且根据乳腺癌基因表达特征的分析可以看出四种亚型之间外显子跳跃数量的显着差异。当涉及肿瘤驱动基因时，TP53 突变和拷贝数丢失的程度在蛋白质结合亚型中最为明显。DNA损伤修复基因中，蛋白结合亚型的RAD54B拷贝数急剧增加，但其他DNA损伤修复相关基因突变较少，拷贝数缺失随处可见。m6A甲基化对浸润免疫细胞比例的影响结果也表明巨噬细胞M0和静息肥大细胞中4个m6A亚群存在显着差异，这与患者预后密切相关。此外，乳腺癌样本中肿瘤干性指数最高、m6A甲基化型指数最低的发现，可以证明m6A reader蛋白的高表达在乳腺癌进展中的关键作用。